The psychoactivity of the root bark of the iboga tree,Tabernanthe iboga, one of the plants from which ibogaine isextracted, was first discovered by thePygmy tribes of Central Africa, who passed the knowledge to theBwiti tribe ofGabon. French explorers, in turn, learned of it from the Bwiti tribe and brought ibogaine back to Europe in 1899–1900, where it was subsequently marketed in France as a stimulant under the trade name Lambarène until the 1960s.[1][2] It was also marketed as Iperton.[2] Ibogaine'santi-addictive properties were first widely promoted in 1962 byHoward Lotsof.
During an 18-year timeline, 19 fatalities temporally associated with the ingestion of ibogaine were reported, from which six subjects died of acute heart failure or cardiopulmonary arrest. Itsprohibition in many countries has slowed scientific research.[9] Various derivatives of ibogaine designed to lack psychedelic properties, such as18-MC, are under preliminary research.
Ibogaine is derived from the root ofTabernanthe iboga, a plant known to exhibitpsychedelic effects in its users.[10] Ibogaine is administered orally at a typical dose of 3–30 mg/kg.Effects first become noticeable 1–3 hours after administration.[11][12] The subjective effects of ibogaine consist of two phases, avisionary phase followed by anintrospective phase.
Thevisionary phase is a dreamlike, conscious state calledoneirophrenia. Visual effects are almost always present and are often described as films or slideshows. These may be accompanied by increases in long-term recall of visual memory, resulting in autobiographical content. Other changes to sensation and perception may occur, including auditory hallucinations or distortions. Nausea and vomiting can be severe. Subjects may experience extreme confusion and/or adepressed mood. Thevisionary stage typically lasts 4–8 hours, but may last longer with especially high doses.[13][14]
Theintrospective is poorly defined, often simply as 24 or 36 hours post-treatment. Sensation and perception return to normal, but nausea, headaches, and other side effects linger. Insomnia, irritability, and mood changes are often seen, including depression and sometimesmania. Depression can persist well after 36 hours, known as a "grey day"; the effect is well-recognized. A persistently low mood can progress intomajor depressive disorder, a chronic condition. For the treatment of opioid or alcohol addiction, the subjective experiences do not appear to be important, although they are correlated to some secondary measures (e.g. satisfaction in self-assessments).[15]
Clinical studies of ibogaine to treat drug addiction began in the early 1990s, but concerns aboutcardiotoxicity terminated those studies.[16] A 2022 review indicated that severeadverse effects, including deaths, have impeded progress toward clinical adoption of ibogaine for use in opioid abstinence.[17] Evidence to determine whether ibogaine is useful for treating addiction is insufficient.[17][18]
Immediate adverse effects of ibogaine ingestion may include nausea, vomiting, tremors leading toataxia, headaches, and mental confusion.[19] In long-term use,manic episodes may last for several days, possibly includinginsomnia, irritability, emotional instability,delusions, aggressive behavior, and thoughts ofsuicide.[19] In the heart, ibogaine causeslong QT syndrome at higher doses, apparently by blockinghERGpotassium channels and slowing theheart rate.[20][21] Ibogaine should not be used during pregnancy or breastfeeding.[19]
Laboratory studies in rats indicate that high-dose ibogaine may cause degeneration ofcerebellarPurkinje cells.[22] However, subsequent research found no evidence ofneurotoxicity in a primate.[23]
In limited human research,neuropathological examination revealed no evidence of neuronal degenerative changes in an adult female patient who had received four separate doses of ibogaine ranging between 10 and 30 mg/kg over a 15-month interval.[23] A published series of fatalities associated with ibogaine ingestion found no evidence for consistent neurotoxicity.[24]
Noribogaine is most potent as aserotonin reuptake inhibitor. It acts as a moderateκ-opioid receptor agonist[31] and weakμ-opioid receptor agonist[31] or weak partial agonist.[32] It is possible that the action of ibogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion;Salvia divinorum, another plant recognized for its strong hallucinogenic properties, contains the chemicalsalvinorin A, which is a highly selective kappa opioid agonist. Noribogaine is more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.[33]
Thebeta-carbolines orharmala alkaloids bear a resemblance to ibogaine both in terms ofchemical structure and subjective effects.[30] Relatedly,harmaline and6-methoxyharmalan fully substitute for ibogaine, whereasharmine,harmane,harmalol, andtryptoline partially substitute for ibogaine.[30][29] As with the case of ibogaine, the psychedelic DOM partially substitutes for harmaline and this further supports a role of serotonin 5-HT2A receptor activation in the effects of ibogaine as well as harmala alkaloids like harmaline.[30]
Ibogaine shows appreciable affinity for theNMDA receptor.[30] However, the NMDA receptor antagonistsphencyclidine (PCP) anddizocilpine (MK-801) fail to substitute for ibogaine and ibogaine fails to substitute for these NMDA receptor antagonists in rodents and/or monkeys.[30][29] Hence, NMDA receptor antagonism does not appear to be involved in the subjective effects of ibogaine.[30][29] Neitherμ-opioid receptor agonists norκ-opioid receptor agonists likeU-50,488 substitute for ibogaine.[30] In addition, theopioid antagonist naloxone did not substitute for ibogaine.[30] However,naltrexone partially substitute for ibogaine.[30] In addition, the mixed opioid agonists and antagonistspentazocine,diprenorphine, andnalorphine partially substituted for ibogaine and this could be antagonized by naloxone.[30] The preceding findings suggest a role ofopioid receptors but not the NMDA receptor in the effects of ibogaine.[30][29]
In contrast to the findings in drug discrimination studies, ibogaine fails to produce thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents.[27][35] As such, it has been said that ibogaine does not appear to be acting primarily or exclusively as a serotonergic psychedelic.[27][35] This is said to be in accordance with its hallucinogenic effects being distinct from those of serotonergic psychedelics.[35][36]
Induction ofgamma oscillations with a profile that resembles that ofREM sleep may be involved in the hallucinogenic and oneirogenic effects of ibogaine.[27][37]
Ibogaine is metabolized in the human body by cytochrome P450 2D6 (CYP2D6) intonoribogaine (more correctly, O-desmethylibogaine or 12-hydroxyibogamine). Both ibogaine and noribogaine have aplasma half-life around two hours in rats,[38] although the half-life of noribogaine is slightly longer than that of the parent compound. Ibogaine may be deposited in fat and metabolized into noribogaine as it is released.[39] After ibogaine ingestion in humans, noribogaine shows higher plasma levels than ibogaine and is detected for a longer period of time than ibogaine.[40]
Ibogaine is asubstituted tryptamine. It has two separatechiral centers, meaning that four different stereoisomers of ibogaine exist, which are difficult toresolve.[41]
One recent total synthesis[42] of ibogaine and related drugs starts with 2-iodo-4-methoxyaniline which is reacted with triethyl((4-(triethylsilyl)but-3-yn-1-yl)oxy)silane usingpalladium acetate inDMF to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and thenfluoride to form 2-(2-iodo-1H-indol-3-yl)ethanol. This is treated withiodine,triphenyl phosphine, andimidazole to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then, using 7-ethyl-2-azabicyclo[2.2.2]oct-5-ene andcesiumcarbonate inacetonitrile, the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclo[2.2.2]oct-5-ene is obtained. Using palladium acetate in DMF, the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclo[2.2.2]octane system in ibogaine is replaced with an endo ethyl, then epiibogaine is formed.
Crystalline ibogaine hydrochloride is typically produced by semisynthesis fromvoacangine in commercial laboratories.[43][44] It can be prepared from voacangine through one-step demethoxycarbonylation process too.[45]
In 2025, researchers at the University of California, Davis Institute for Psychedelics and Neurotherapeutics reported the total synthesis of ibogaine, ibogaine analogues, and related compounds frompyridine.[46][47]
A synthetic derivative of ibogaine,18-methoxycoronaridine (18-MC), is a selective α3β4 antagonist that was developed collaboratively by neurologist Stanley D. Glick (Albany) and chemist Martin E. Kuehne (Vermont).[48] This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine, such ascoronaridine andvoacangine, that showed these compounds to have anti-addictive properties.[49][50] More recently, non- and less-hallucinogenic analogs,tabernanthalog and ibogainalog, were engineered by scientists attempting to produce non-cardiotoxic ibogaine derivatives by removing thelipophilic isoquinuclidine ring. In animal models, both molecules failed to producecardiac arrhythmias, and tabernanthalog failed to produce any head twitch response, suggesting psychedelic effects were absent.[51][52]
Ibogaine biosynthesis begins with tryptophan undergoing enzymatic decarboxylation by tryptophan decarboxylase (TDC) to form a tryptamine. Secologanin, an iridoid synthesized from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), is reacted with tryptamine to make strictosidine. A glycosidic bond cleavage of strictosidine by strictosidine β-deglucosidase (SGD) produces a lactol. The lactol opens and produces an aldehyde, then condenses to form an iminium. Through isomerization and reduction by geissoschizine synthase 1 (GS1), 19E-geissoschizine is yielded. The indole is oxidized and the molecule undergoes intramolecular Mannich reaction and Grob fragmentation to form preakuammicine. Preakuammicine is highly unstable and therefore reduced to stemmadenine by oxidation-reduction reactions (REDOX 1 and REDOX 2). Stemmadine is acylated by stemmadine Ο-acetyltransferase (SAT) to yield stemmadine acetate. Through oxidation by precondylocarpine acetate synthase (PAS) and reduction by dihydroprecondylocarpine acetate synthase (DPAS), an enamine intermediate is formed. The intermediate undergoes fragmentation to produce an iminium that tautomerizes to yield dehydrosecodine. Coronaridine synthase (CorS) catalyzes the isomerization of dehydrosecodine and an unusual cycloaddition is completed. The iminium is reduced by DPAS and NADPH to form (-)-coronaridine.[citation needed]
There are two pathways (-)-coronaridine can take to become (-)-ibogaine. The first pathway begins with a P450 enzyme, ibogamine-10-hydroxylase (I10H), and methylation of noribogaine-10-Ο-methyltransferase (N10OMT) to produce (-)-voacangine. Polyneudridine aldehyde esterase-like 1 (PNAE1) and a spontaneous decarboxylation can convert (-)-voacangine to (-)-ibogaine. The second pathway consists of PNAE1 and the spontaneous decarboxylation occurring first to yield (-)-ibogamine, then the reaction of I10H-mediated hydroxylation and N10OMT-catalyzed O-methylation to produce (-)-ibogaine.[53]
Ibogaine occurs naturally in iboga root bark. Ibogaine is also available in a total alkaloid extract of theTabernanthe iboga plant, which also contains all the other iboga alkaloids and thus has only about half the potency by weight of standardized ibogaine hydrochloride.[43]
The use of iboga in African spiritual ceremonies was first reported by French and Belgian explorers in the 19th century, beginning with the work of French naval physician andexplorer ofGabonMarie-Théophile Griffon du Bellay.[54] The first botanical description of theTabernanthe iboga plant was made in 1889. Ibogaine was first isolated fromT.iboga in 1901 by Dybowski and Landrin[55] and independently by Haller and Heckel in the same year usingT. iboga samples fromGabon. Complete synthesis of ibogaine was accomplished by G. Büchi in 1966.[56] Since then, several other synthesis methods have been developed.[57]
From the 1930s to 1960s, ibogaine was sold in France in the form of Lambarène, an extract of theTabernanthe manii plant, and promoted as a mental and physical stimulant.[1] It was formulated at doses of 200mg extract containing low doses of 4 to 8mg ibogaine per tablet.[2][1] The drug enjoyed some popularity among post-World War II athletes. Lambarène was withdrawn from the market in 1966 when the sale of ibogaine-containing products became illegal in France.[58][1] Another formulation was Iperton, which containedTabernanthe iboga extract 40mg per dose unit.[2]
Anecdotal reports concerning ibogaine's effects appeared in the early 1960s.[59] Its anti-addictive properties were discovered accidentally byHoward Lotsof in 1962, at the age of 19, when he and five friends—all heroin addicts—noted subjective reduction of their craving andwithdrawal symptoms while taking it.[60] Further anecdotal observation convinced Lotsof of its potential usefulness in treating substance addictions. He contracted with a Belgian company to produce ibogaine in tablet form for clinical trials in the Netherlands, and was awarded a United States patent for the product in 1985. The first objective, placebo-controlled evidence of ibogaine's ability to attenuate opioid withdrawal in rats was published by Dzoljicet al. in 1988.[61] Diminution ofmorphine self-administration was reported in preclinical studies by Glicket al. in 1991.[62] Cappendijket al. demonstrated reduction incocaine self-administration in rats in 1993,[63] and Rezvani reported reducedalcohol dependence in three strains of "alcohol-preferring" rats in 1995.[64]
As the use of ibogaine spread, its administration varied widely; some groups administered it systematically using well-developed methods and medical personnel, while others employed haphazard and possibly dangerous methodology. Lotsof and his colleagues, committed to the traditional administration of ibogaine, developed treatment regimens themselves. In 1992, Eric Taub brought ibogaine to an offshore location close to the United States, where he began providing treatments and popularizing its use.[65] InCosta Rica, Lex Kogan, another leading proponent, joined Taub in systematizing its administration. The two men established medically monitored treatment clinics in several countries.[66]
In 1981, an unnamed European manufacturer produced 44 kg of iboga extract. The entire stock was purchased by Carl Waltenburg, who distributed it under the name "Indra extract" and used it in 1982 to treat heroin addicts in the community ofChristiania.[10] Indra extract was available for sale over the Internet until 2006, when the Indra web presence disappeared. Various products are currently sold in a number of countries as "Indra extract", but it is unclear if any of them are derived from Waltenburg's original stock. Ibogaine and relatedindole compounds are susceptible tooxidation over time.[67][68]
TheNational Institute on Drug Abuse (NIDA) began funding clinical studies of ibogaine in the United States in the early 1990s, but terminated the project in 1995.[69] Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alperet al. in 1999.[70] A cohort of 33 patients were treated with 6 to 29 mg/kg of ibogaine; 25 displayed resolution of the signs of opioid withdrawal from 24 hours to 72 hours post-treatment, but one 24-year-old female, who received the highest dosage, died. Mashet al. (2000), using lower oral doses (10–12 mg/kg) in 27 patients, demonstrated significantly lower objective opiate withdrawal scores in heroin addicts 36 hours after treatment, with self-reports of decreased cocaine and opiate craving and alleviated depression symptoms. Many of these effects appeared sustainable over a one-month post-discharge follow-up.[71]
As of 2024[update], the legal status of ibogaine varies widely among countries, as it may be illegal to possess or use, may be legalized, may bedecriminalized, or is under consideration for future legislation.[72]
Ibogaine treatment clinics have emerged inMexico,Bahamas,Canada, theNetherlands,South Africa, andNew Zealand, all operating in what has been described as a "legal gray area".[74][75]Costa Rica also has treatment centers.[66] Covert, illegal neighborhood clinics are known to exist in the United States, despite activeDEA surveillance.[76] While clinical guidelines for ibogaine-assisted detoxification were released by the Global Ibogaine Therapy Alliance in 2015,[77][78] addiction specialists warn that the treatment of drug dependence with ibogaine in non-medical settings, without expert supervision and unaccompanied by appropriate psychosocial care, can be dangerous — and, in approximately one case in 300, potentially fatal.[75]
Detox or Die [d] (2004). Directed by David Graham Scott. Scott begins videotaping his heroin-addicted friends. Before long, he himself is addicted to the drug. He eventually turns the camera on himself and his family. After 12 years of debilitating, painful dependence on methadone, Scott turns to ibogaine. Filmed in Scotland and England, and broadcast onBBC One as the third installment in the documentary seriesOne Life.[79]
Ibogaine: Rite of Passage [d] (2004). Directed by Ben Deloenen. Cy, a 34-year-old heroin addict, undergoes ibogaine treatment with Dr. Martin Polanco at the Ibogaine Association, a clinic in Rosarito, Mexico. Deloenen interviews people formerly addicted to heroin, cocaine, and methamphetamine, who share their perspectives about ibogaine treatment. In Gabon, aBabongo woman receives iboga root for her depressive malaise. Deloenen visually contrasts this Western, clinical use of ibogaine with the Bwiti use of iboga root, but emphasizes the Western context.[80]
Facing the Habit [d] (2007). Directed by Magnolia Martin. Martin's subject is a former millionaire and stockbroker who travels to Mexico for ibogaine treatment for heroin addiction.[81]
Tripping in Amsterdam (2008). In this short film directed by Jan Bednarz, Simon "Swany" Wan visits Sara Glatt's iboga treatment center in Amsterdam.[82]Current TV broadcast the documentary in 2008 as part of their "Quarter-life Crisis" programming roster.
One of the five segments of "Hallucinogens DMT" (2012),Season 2, Episode 4 ofDrugs, Inc. onNational Geographic Channel, a former heroin user treats addicts with ibogaine in Canada. He himself used ibogaine to stop his abuse of narcotics.[citation needed]
The "Underground Heroin Clinic" segment of "Addiction" (2013).Season 1, episode 7 of theHBO documentary seriesVice examines the use of ibogaine to interrupt heroin addiction.[84][85]
The Ibogaine Safari (2014). A documentary by filmmaker Pierre le Roux which investigates the claims of painless withdrawal from opiates such asnyaope/heroin in South Africa by taking several addicts on an adventure "safari" while taking ibogaine. The documentary won the award for 'Best Documentary Short' at the 2014Canada International Film Festival.[86][87]
Dosed [d] (2019). A documentary by Tyler Chandler and Nicholas Meyers. Synopsis- After years of no success with prescription drugs, a suicidal Adrianne seeks help from underground healers with her depression, anxiety, and opioid addiction by utilizing illegal psychedelics like magic mushrooms and iboga.[89]
"Synthetic Ibogaine - Natural Tramadol" (2021). This episode of the documentary seriesHamilton's Pharmacopeia onVice on TV, follows a struggling local addict to an ibogaine ritual.[90]
Author and musicianGeoff Rickly based his debut novelSomeone Who Isn't Me on his real-life experiences with heroin addiction and an ibogaine clinic in Mexico.[98]
American investigative journalist,Rachel Nuwer, published a comprehensive feature forReason magazine titledCan This Psychedelic Help Cure Opioid Addiction?[99] In the article, Rachel speaks with experts in the field ofopioid use disorder (OUD) and how ibogaine shows promising results for effective treatment and recovery. This is particularly true for those patients that also suffer fromtraumatic brain injuries (TBI).[100]
"Sink or Swim. Act Two. I'm Not a Doctor But I Play One at the Holiday Inn.".This American Life. Episode 321. 1 December 2006. — A former heroin addict realizes that he wants to help other addicts kick their habits. The problem is, he wants to do this using a hallucinogenic drug - ibogaine - that is completely illegal, and which requires medical expertise he doesn't have.[101]
In January 2025, formerTexas GovernorRick Perry and W. Bryan Hubbard, appeared onThe Joe Rogan Experience. The trio discussed advances in public policy towards ibogaine and eventual FDA clinical trials.[102][103] Hubbard was the former Chairman and Executive Director of the Kentucky Opioid Abatement Advisory Commission until he was asked to resign in December 2023.[104] Since 2024, Hubbard has continued his campaign outside Kentucky and now works with the REID Foundation as the Executive Director of the American Ibogaine Initiative.[105]
The most-studied therapeutic effect of ibogaine is the possible reduction or elimination ofaddiction toopioids. Research suggests that ibogaine may be useful in treating dependence on other substances such asalcohol,methamphetamine, andnicotine, and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence.[medical citation needed] Researchers note that there remains a "need for systematic investigation in a conventional clinical research setting."[59]
Many users of ibogaine report experiencing visual phenomena during a waking dream state, such as instructive replays of life events that led to their addiction, while others report therapeuticshamanic visions that help them conquer the fears andnegative emotions that might drive their addiction. It is proposed that intensive counseling, therapy, and aftercare during the interruption period following treatment is of significant value. Some individuals require a second or third treatment session with ibogaine over the course of 12 to 18 months. A minority of individuals relapse completely into opiate addiction within days or weeks.[106]
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